Bioreactor with impeller assembly

CROSS-REFERENCE TO RELATED APPLICATIONS

This application is a continuation of U.S. application Ser. No. 14/660,405, filed Mar. 17, 2015, which claims priority to U.S. Provisional Patent Application No. 61/969,094 filed Mar. 22, 2014, which are incorporated herein by specific reference.

BACKGROUND OF THE INVENTION

1. The Field of the Invention

The present invention relates to bioreactors having an impeller assembly.

2. The Relevant Technology

The biopharmaceutical industry uses a broad range of mixing systems for a variety of processes such as in the preparation of media and buffers and in the growing, mixing and suspension of cells and microorganisms. Some conventional mixing systems, including bioreactors and fermentors, comprise a flexible bag disposed within a rigid support housing. An impeller is disposed within the flexible bag and is coupled with a drive shaft projecting into the bag. Rotation of the drive shaft and impeller facilitates mixing and/or suspension of the fluid contained within the flexible bag.

Although the current mixing systems are useful, they have some limitations. For example, where the drive shaft is secured within the flexible bag during the manufacturing process, the rigid drive shaft limits the ability to collapse or fold the flexible bag so as to reduce its size for transportation, storage and/or further processing. Likewise, where it is intended to reuse the drive shaft, such as when it is made of metal, this system has the disadvantage of needing to clean and sterilize the drive shaft between different uses.

In an alternative mixing system, a flexible tube is disposed within a flexible bag. A first end of the tube is rotatably coupled by a dynamic seal to the bag while an opposing second end of the tube is sealed to an impeller. During use, a rigid drive shaft is passed down into the tube and couples with the impeller. In turn, rotation of the drive shaft facilitates rotation of the tube and impeller for mixing the fluid within the flexible bag. In this design, before the drive shaft is inserted, the combined flexible bag and tube can be folded for ease of storage and transportation. In addition, the tube isolates the drive shaft from the fluid so that during use the drive shaft does not directly contact the fluid within the bag. As such, following use, the drive shaft can be removed and reused without the need for cleaning or sterilization.

Although the mixing system using the flexible tube has a number of improved advantages, it also has some limitations. For example, the flexible tube design is limited to a single impeller mounted on the end thereof. In larger volume mixing systems or in applications where higher rates of mixing are required, a single impeller may not be sufficient to achieve a needed mixing rate. Accordingly, what is needed in the art are mixing systems that retain all or some of the advantages of using the flexible tube to isolate the rigid drive shaft from the fluid but enable higher mixing rates relative to the single impeller design.

BRIEF DESCRIPTION OF THE DRAWINGS

To further clarify the above and other advantages and features of the present invention, a more particular description of the invention will be rendered by reference to specific embodiments thereof which are illustrated in the appended drawings. It is appreciated that these drawings depict only illustrated embodiments of the invention and are therefore not to be considered limiting of its scope. The invention will be described and explained with additional specificity and detail through the use of the accompanying drawings in which:

<figref idref="DRAWINGS">FIG. 1</figref> is a perspective view of a fluid mixing system;

<figref idref="DRAWINGS">FIG. 2</figref> is a perspective view of the container assembly and drive motor assembly of the fluid mixing system shown in <figref idref="DRAWINGS">FIG. 1</figref>;

<figref idref="DRAWINGS">FIG. 3</figref> is a perspective view of the impeller assembly, drive shaft and drive motor shown in <figref idref="DRAWINGS">FIG. 2</figref>;

<figref idref="DRAWINGS">FIG. 4</figref> is a perspective view of the drive shaft in <figref idref="DRAWINGS">FIG. 3</figref> being coupled with the drive motor assembly;

<figref idref="DRAWINGS">FIG. 5</figref> is an elevated side view of the impeller assembly and drive shaft shown in <figref idref="DRAWINGS">FIG. 3</figref>;

<figref idref="DRAWINGS">FIG. 6</figref> is an enlarged top perspective view of the rotational assembly shown in <figref idref="DRAWINGS">FIG. 5</figref>;

<figref idref="DRAWINGS">FIG. 7</figref> is an exploded perspective view of the second tubular connector and impellers shown in <figref idref="DRAWINGS">FIG. 5</figref>;

<figref idref="DRAWINGS">FIG. 8</figref> is an enlarged exploded perspective view of the first end of the second tubular connector and an impeller to be received thereon;

<figref idref="DRAWINGS">FIG. 9</figref> is a perspective view of the components in <figref idref="DRAWINGS">FIG. 8</figref> assembled;

<figref idref="DRAWINGS">FIG. 10</figref> is an enlarged exploded perspective view of the second end of the second tubular connector and an end cap to be received thereon;

<figref idref="DRAWINGS">FIG. 11</figref> is a cross sectional side view of the second tubular connector with the impellers thereon; and

<figref idref="DRAWINGS">FIG. 12</figref> is an elevated side view of an alternative embodiment of a drive shaft.

DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

Before describing the present disclosure in detail, it is to be understood that this disclosure is not limited to particularly exemplified apparatus, systems, methods, or process parameters that may, of course, vary. It is also to be understood that the terminology used herein is only for the purpose of describing particular embodiments of the present disclosure, and is not intended to limit the scope of the invention.

All publications, patents, and patent applications cited herein, whether supra or infra, are hereby incorporated by reference in their entirety to the same extent as if each individual publication, patent, or patent application was specifically and individually indicated to be incorporated by reference.

The term “comprising” which is synonymous with “including,” “containing,” “having” or “characterized by,” is inclusive or open-ended and does not exclude additional, unrecited elements or method steps.

It will be noted that, as used in this specification and the appended claims, the singular forms “a,” “an” and “the” include plural referents unless the content clearly dictates otherwise. Thus, for example, reference to a “port” includes one, two, or more ports.

As used in the specification and appended claims, directional terms, such as “top,” “bottom,” “left,” “right,” “up,” “down,” “upper,” “lower,” “inner,” “outer,” “internal,” “external,” “interior,” “exterior,” “proximal,” “distal” and the like are used herein solely to indicate relative directions and are not otherwise intended to limit the scope of the invention or claims.

Where possible, like numbering of elements have been used in various figures. Furthermore, alternative configurations of a particular element may each include separate letters appended to the element number. Accordingly, an appended letter can be used to designate an alternative design, structure, function, implementation, and/or embodiment of an element or feature without an appended letter. For instance, an element “<b>80</b>” may be embodied in an alternative configuration and designated “<b>80</b><i>a</i>.” Similarly, multiple instances of an element and or sub-elements of a parent element may each include separate letters appended to the element number. In each case, the element label may be used without an appended letter to generally refer to instances of the element or any one of the alternative elements. Element labels including an appended letter can be used to refer to a specific instance of the element or to distinguish or draw attention to multiple uses of the element.

Various aspects of the present devices, systems, and methods may be illustrated with reference to one or more exemplary embodiments. As used herein, the term “embodiment” means “serving as an example, instance, or illustration,” and should not necessarily be construed as preferred or advantageous over other embodiments disclosed herein.

Various aspects of the present devices and systems may be illustrated by describing components that are coupled, attached, and/or joined together. As used herein, the terms “coupled”, “attached”, “connected” and/or “joined” are used to indicate either a direct connection between two components or, where appropriate, an indirect connection to one another through intervening or intermediate components. In contrast, when a component is referred to as being “directly coupled”, “directly attached”, “directly connected” and/or “directly joined” to another component, there are no intervening elements present.

Unless defined otherwise, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which the present disclosure pertains. Although a number of methods and materials similar or equivalent to those described herein can be used in the practice of the present disclosure, the preferred materials and methods are described herein.

The present invention relates to fluid processing systems and related methods for mixing and sparging solutions and/or suspensions. The processing systems can be bioreactors or fermentors used for culturing cells or microorganisms. By way of example and not by limitation, the inventive systems can be used in culturing bacteria, fungi, algae, plant cells, animal cells, protozoans, nematodes, and the like. The systems can accommodate cells and microorganisms that are aerobic or anaerobic and are adherent or non-adherent. The systems can also be used in association with the formation and/or treatment of solutions and/or suspensions that are not biological but nevertheless incorporate mixing. For example, the systems can be used in the production of media, chemicals, food products, beverages, and other liquid products.

The inventive systems are designed so that a majority of the system components that contact the material being processed can be disposed of after each use. As a result, the inventive systems substantially eliminate the burden of cleaning and sterilization required by conventional stainless steel mixing and processing systems. This feature also ensures that sterility can be consistently maintained during repeated processing of multiple batches. In view of the foregoing, and the fact that the inventive systems are easily scalable, relatively low cost, and easily operated, the inventive systems can be used in a variety of industrial and research facilities that previously outsourced such processing.

Depicted in <figref idref="DRAWINGS">FIG. 1</figref> is one embodiment of an inventive fluid processing system <b>10</b> incorporating features of the present invention. In general, processing system <b>10</b> comprises a container <b>12</b> that is disposed within a rigid support housing <b>14</b>. A mixer system <b>18</b> is designed for mixing and/or suspending components within container <b>12</b>. The various components of fluid processing system <b>10</b> will now be discussed in greater detail.

With continued reference to <figref idref="DRAWINGS">FIG. 1</figref>, support housing <b>14</b> has a substantially cylindrical sidewall <b>20</b> that extends between an upper end <b>22</b> and an opposing lower end <b>24</b>. Lower end <b>24</b> has a floor <b>26</b> mounted thereto. Support housing <b>14</b> has an interior surface <b>28</b> that bounds a chamber <b>30</b>. An annular lip <b>32</b> is formed at upper end <b>22</b> and bounds an opening <b>34</b> to chamber <b>30</b>. Floor <b>26</b> of support housing <b>14</b> rests on a cart <b>36</b> having wheels <b>38</b>. Support housing <b>14</b> is removably secured to cart <b>36</b> by connectors <b>40</b>. Cart <b>36</b> enables selective movement and positioning of support housing <b>14</b>. In alternative embodiments, however, support housing <b>14</b> need not rest on cart <b>36</b> but can rest directly on a floor or other structure.

Although support housing <b>14</b> is shown as having a substantially cylindrical configuration, in alternative embodiments support housing <b>14</b> can have any desired shape capable of at least partially bounding a compartment. For example, sidewall <b>20</b> need not be cylindrical but can have a variety of other transverse, cross sectional configurations such as polygonal, elliptical, or irregular. Furthermore, it is appreciated that support housing <b>14</b> can be scaled to any desired size. For example, it is envisioned that support housing <b>14</b> can be sized so that chamber <b>30</b> can hold a volume of less than 50 liters or more than 1,000 liters. Support housing <b>14</b> is typically made of metal, such as stainless steel, but can also be made of other materials capable of withstanding the applied loads of the present invention.

In one embodiment of the present invention means are provided for regulating the temperature of the fluid that is contained within container <b>12</b> disposed within support housing <b>14</b>. By way of example and not by limitation, electrical heating elements can be mounted on or within support housing <b>14</b>. The heat from the heating elements is transferred either directly or indirectly to container <b>12</b>. Alternatively, in the depicted embodiment support housing <b>14</b> is jacketed with one or more fluid channels being formed therein. The fluid channels have a fluid inlet <b>42</b> and a fluid outlet <b>44</b> that enables a fluid, such as water or propylene glycol, to be pumped through the fluid channels. By heating, cooling or otherwise controlling the temperature of the fluid that is passed through the fluid channels, the temperature of support housing <b>14</b> can be regulated which in turn regulates the temperature of the fluid within container <b>12</b> when container <b>12</b> is disposed within support housing <b>14</b>. Other conventional means can also be used such as by applying gas burners to support housing <b>14</b> or pumping the fluid out of container <b>12</b>, heating or cooling the fluid and then pumping the fluid back into container <b>12</b>. When using container <b>12</b> as part of a bioreactor or fermentor, the means for heating can be used to heat the culture within container <b>12</b> to a temperature in a range between about 30° C. to about 40° C. Other temperatures can also be used.

Support housing <b>14</b> can have one or more openings <b>46</b> formed on the lower end of sidewall <b>20</b> and on floor <b>26</b> to enable gas and fluid lines to couple with container <b>12</b> and to enable various probes and sensors to couple with container <b>12</b> when container <b>12</b> is within support housing <b>14</b>. Further disclosure on support housing <b>14</b> and alternative designs thereof is disclosed in U.S. Pat. No. 7,682,067 and US Patent Publication No. 2011-0310696, which are incorporated herein by specific reference.

<figref idref="DRAWINGS">FIG. 2</figref> shows container <b>12</b> coupled with mixer system <b>18</b>. Container <b>12</b> has a side <b>55</b> that extends from an upper end <b>56</b> to an opposing lower end <b>57</b>. Container <b>12</b> also has an interior surface <b>58</b> that bounds a compartment <b>50</b> in which a portion of mixer system <b>18</b> is disposed. In the embodiment depicted, container <b>12</b> comprises a flexible bag. Formed on container <b>12</b> are a plurality of ports <b>51</b> that communicate with compartment <b>50</b>. Although only two ports <b>51</b> are shown, it is appreciated that container <b>12</b> can be formed with any desired number of ports <b>51</b> and that ports <b>51</b> can be formed at any desired location on container <b>12</b> such as upper end <b>56</b>, lower end <b>57</b>, and/or alongside <b>55</b>. Ports <b>51</b> can be the same configuration or different configurations and can be used for a variety of different purposes. For example, ports <b>51</b> can be coupled with fluid lines for delivering media, cell cultures, and/or other components into and out of container <b>12</b>.

Ports <b>51</b> can also be used for coupling probes to container <b>12</b>. For example, when container <b>12</b> is used as a bioreactor for growing cells or microorganisms, ports <b>51</b> can be used for coupling probes such as temperatures probes, pH probes, dissolved oxygen probes, and the like. Examples of ports <b>51</b> and how various probes and lines can be coupled thereto is disclosed in United States Patent Publication No. 2006-0270036, published Nov. 30, 2006 and United States Patent Publication No. 2006-0240546, published Oct. 26, 2006, which are incorporated herein by specific reference. Ports <b>51</b> can also be used for coupling container <b>12</b> to secondary containers and to other desired fittings.

In one embodiment of the present invention, means are provided for delivering a gas into the lower end of container <b>12</b>. By way of example and not by limitation, as also depicted in <figref idref="DRAWINGS">FIG. 2</figref>, a sparger <b>54</b> can be either positioned on or mounted to lower end <b>57</b> of container <b>12</b> for delivering a gas to the fluid within container <b>12</b>. As is understood by those skilled in the art, various gases are typically required in the growth of cells or microorganisms within container <b>12</b>. The gas typically comprises air that is selectively combined with oxygen, carbon dioxide and/or nitrogen. However, other gases can also be used. The addition of these gases can be used to regulate the dissolved oxygen and CO₂content and to regulate the pH of a culture solution. Depending on the application, sparging with gas can also have other applications. A gas line <b>61</b> is coupled with sparger <b>54</b> for delivering the desired gas to sparger <b>54</b>. Gas line <b>61</b> need not pass through lower end <b>57</b> of container <b>12</b> but can extend down from upper end <b>56</b> or from other locations.

Sparger <b>54</b> can have a variety of different configurations. For example, sparger <b>54</b> can comprise a permeable membrane or a fritted structure comprised of metal, plastic or other materials that dispense the gas in small bubbles into container <b>12</b>. Smaller bubbles can permit better absorption of the gas into the fluid. In other embodiments, sparger <b>54</b> can simply comprise a tube, port, or other type opening formed on or coupled with container <b>12</b> through which gas is passed into container <b>12</b>. In contrast to being disposed on container <b>12</b>, the sparger can also be formed on or coupled with mixer system <b>18</b>. Examples of spargers and how they can be used in the present invention are disclosed in United States Patent Publication Nos. 2006-0270036 and 2006-0240546 which were previously incorporated by reference. Other conventional spargers can also be used. It is appreciated that in some embodiments and uses that a sparger may not be required.

In the depicted embodiment, container <b>12</b> has an opening <b>52</b> that is sealed to a rotational assembly <b>82</b> of mixer system <b>18</b>, which will be discussed below in greater detail. As a result, compartment <b>50</b> is sealed closed so that it can be sterilized and be used in processing sterile fluids. During use, container <b>12</b> is disposed within chamber <b>30</b> of support housing <b>14</b> as depicted in <figref idref="DRAWINGS">FIG. 1</figref>. Container <b>12</b> is supported by support housing <b>14</b> during use and can subsequently be disposed of following use. In one embodiment, container <b>12</b> is comprised of a flexible, water impermeable material such as a low-density polyethylene or other polymeric sheets or film having a thickness in a range between about 0.1 mm to about 5 mm with about 0.2 mm to about 2 mm being more common. Other thicknesses can also be used. The material can be comprised of a single ply material or can comprise two or more layers which are either sealed together or separated to form a double wall container. Where the layers are sealed together, the material can comprise a laminated or extruded material. The laminated material comprises two or more separately formed layers that are subsequently secured together by an adhesive.

The extruded material comprises a single integral sheet that comprises two or more layers of different materials that can be separated by a contact layer. All of the layers are simultaneously co-extruded. One example of an extruded material that can be used in the present invention is the Thermo Scientific CX3-9 film available from Thermo Fisher Scientific. The Thermo Scientific CX3-9 film is a three-layer, 9 mil cast film produced in a cGMP facility. The outer layer is a polyester elastomer coextruded with an ultra-low density polyethylene product contact layer. Another example of an extruded material that can be used in the present invention is the Thermo Scientific CX5-14 cast film also available from Thermo Fisher Scientific. The Thermo Scientific CX5-14 cast film comprises a polyester elastomer outer layer, an ultra-low density polyethylene contact layer, and an EVOH barrier layer disposed therebetween.

The material is approved for direct contact with living cells and is capable of maintaining a solution sterile. In such an embodiment, the material can also be sterilizable such as by radiation. Examples of materials that can be used in different situations are disclosed in U.S. Pat. No. 6,083,587 which issued on Jul. 4, 2000 and United States Patent Publication No. US 2003-0077466 A1, published Apr. 24, 2003, which are hereby incorporated by specific reference.

In one embodiment, container <b>12</b> comprises a two-dimensional pillow style bag wherein two sheets of material are placed in overlapping relation and the two sheets are bounded together at their peripheries to form the internal compartment. Alternatively, a single sheet of material can be folded over and seamed around the periphery to form the internal compartment. In another embodiment, the containers can be formed from a continuous tubular extrusion of polymeric material that is cut to length and is seamed closed at the ends.

In still other embodiments, container <b>12</b> can comprise a three-dimensional bag that not only has an annular side wall but also a two dimensional top end wall and a two dimensional bottom end wall. Three dimensional containers comprise a plurality of discrete panels, typically three or more, and more commonly four or six. Each panel is substantially identical and comprises a portion of the side wall, top end wall, and bottom end wall of the container. Corresponding perimeter edges of each panel are seamed together. The seams are typically formed using methods known in the art such as heat energies, RF energies, sonics, or other sealing energies.

In alternative embodiments, the panels can be formed in a variety of different patterns. Further disclosure with regard to one method of manufacturing three-dimensional bags is disclosed in United States Patent Publication No. US 2002-0131654 A1, published Sep. 19, 2002, which is hereby incorporated by reference.

It is appreciated that container <b>12</b> can be manufactured to have virtually any desired size, shape, and configuration. For example, container <b>12</b> can be formed having a compartment sized to 10 liters, 30 liters, 100 liters, 250 liters, 500 liters, 750 liters, 1,000 liters, 1,500 liters, 3,000 liters, 5,000 liters, 10,000 liters or other desired volumes. The size of the compartment can also be in the range between any two of the above volumes. Although container <b>12</b> can be any shape, in one embodiment container <b>12</b> is specifically configured to be complementary or substantially complementary to chamber <b>30</b> of support housing <b>14</b>. It is desirable that when container <b>12</b> is received within chamber <b>30</b>, container <b>12</b> is at least generally uniformly supported by support housing <b>14</b>. Having at least general uniform support of container <b>12</b> by support housing <b>14</b> helps to preclude failure of container <b>12</b> by hydraulic forces applied to container <b>12</b> when filled with fluid.

Although in the above discussed embodiment container <b>12</b> has a flexible, bag-like configuration, in alternative embodiments it is appreciated that container <b>12</b> can comprise any form of collapsible container or semi-rigid container. Container <b>12</b> can also be transparent or opaque and can have ultraviolet light inhibitors incorporated therein.

Mixer system <b>18</b> is used for mixing and/or suspending a culture or other solution or suspension within container <b>12</b>. As depicted in <figref idref="DRAWINGS">FIG. 2</figref>, mixer system <b>18</b> generally comprises a drive motor assembly <b>59</b> that is mounted on support housing <b>14</b> (<figref idref="DRAWINGS">FIG. 1</figref>), an impeller assembly <b>78</b> coupled to and projecting into container <b>12</b>, and a drive shaft <b>72</b> (<figref idref="DRAWINGS">FIG. 4</figref>) that extends between drive motor assembly <b>59</b> and impeller assembly <b>78</b>.

Turning to <figref idref="DRAWINGS">FIG. 3</figref>, drive motor assembly <b>59</b> comprises a housing <b>60</b> having a top surface <b>62</b> and an opposing bottom surface <b>64</b> with an opening <b>66</b> extending through housing <b>60</b> between surfaces <b>62</b> and <b>64</b>. A tubular motor mount <b>68</b> is rotatably secured within opening <b>66</b> of housing <b>60</b> and bounds a passage <b>90</b> extending therethrough. As depicted in <figref idref="DRAWINGS">FIG. 4</figref>, the upper end of motor mount <b>68</b> terminates at an ends face <b>92</b> having a locking pin <b>94</b> outwardly projecting therefrom. A thread <b>96</b> encircles motor mount <b>68</b> adjacent to end face <b>92</b>. Returning to <figref idref="DRAWINGS">FIG. 3</figref>, a drive motor <b>70</b> is mounted to housing <b>60</b> and engages with motor mount <b>68</b> so as to facilitate select rotation of motor mount <b>68</b> relative to housing <b>60</b>. As depicted in <figref idref="DRAWINGS">FIG. 1</figref>, drive motor assembly <b>59</b> is coupled with support housing <b>14</b> by a bracket <b>53</b>. In alternative embodiments, however, drive motor assembly <b>59</b> can be mounted on a separate structure adjacent to support housing <b>14</b>.

Drive shaft <b>72</b> is configured to pass through motor mount <b>68</b> and thus through housing <b>60</b>. Turning to <figref idref="DRAWINGS">FIG. 5</figref>, drive shaft <b>72</b> has a first end <b>98</b> and an opposing second end <b>100</b> and generally comprises a shaft portion <b>101</b> with a head <b>103</b> mounted on the end thereof. Head <b>103</b> includes a substantially frustoconical engaging portion <b>102</b> that is complimentary to an engaging portion formed within the upper end of motor mount <b>68</b>. As a result, the two engaging portions can be complementary mated to facilitate contacting engagement between motor mount <b>68</b> and drive shaft <b>72</b> when drive shaft <b>72</b> is passed through motor mount <b>68</b>.

As depicted in <figref idref="DRAWINGS">FIG. 4</figref>, head <b>103</b> also includes a substantially circular plate <b>104</b> disposed on top of engaging portion <b>102</b>. Plate <b>104</b> extends to a perimeter edge <b>106</b> that radially outwardly projects beyond engaging portion <b>102</b>. A plurality of spaced apart notches <b>108</b> are formed on perimeter edge <b>106</b>. When drive shaft <b>72</b> is passed through motor mount <b>68</b>, plate <b>104</b> rests on or slightly above end face <b>92</b> of motor mount <b>68</b> so that locking pin <b>94</b> is received within a notch <b>108</b>. As a result, drive shaft <b>72</b> is locked to motor mount <b>68</b> so that rotation of motor mount <b>68</b> facilitates concurrent rotation of drive shaft <b>72</b>. A cap <b>115</b> (<figref idref="DRAWINGS">FIG. 3</figref>) can be threaded onto the end of motor mount <b>70</b> to prevent drive shaft <b>72</b> from disengaging from motor mount <b>70</b>.

Returning to <figref idref="DRAWINGS">FIG. 5</figref>, shaft portion <b>101</b> comprises a first driver portion <b>112</b> and a second driver portion <b>114</b>. Driver portions <b>112</b> and <b>114</b>, as will be discussed below in greater detail, typically have a polygonal transverse cross section. For example, driver portions <b>112</b> and <b>114</b> can have 5, 6, 7, or more sides. In other embodiments, the transverse cross of section of driver portions <b>112</b> and <b>114</b> can be other non-circular shapes such as oval or irregular. The remainder of shaft portion <b>101</b> typically has a circular transverse cross section with a maximum diameter that is smaller than the maximum diameter of driver portions <b>112</b> and <b>114</b>. Second end <b>100</b> of drive shaft <b>72</b> terminates at a nose <b>105</b> that is inwardly tapered for easy insertion.

In one embodiment drive shaft <b>72</b> can comprise a single, unitary shaft. In other embodiments, draft shaft <b>72</b> can be comprised of multiple sections that are selectively threaded or otherwise secured together. For example, drive shaft can comprise a head section <b>74</b> and a separate shaft section <b>76</b> that can be coupled together as depicted in <figref idref="DRAWINGS">FIG. 3</figref>. Drive shaft <b>72</b> can be formed from 2, 3, 4, 5 or more sections that are selectively coupled together. Drive shaft <b>72</b> can be comprised of high strength polymers, ceramics, composites, metals, such as aluminum, stainless steel, or other metal alloys, or other materials. Furthermore, different sections can be made of different materials.

By forming drive shaft <b>72</b> from multiple sections, it is easy to form a shaft having a desired length by adding or removing sections. Furthermore, the modular drive shaft <b>72</b> can be used in a room with a low ceiling height. For example, a first section of drive shaft <b>72</b> can be partially advanced down through motor mount <b>68</b>. Additional sections can then be progressively attached thereto as the sections are progressively advanced down through motor mount <b>68</b>. Accordingly, the full length of drive shaft <b>72</b> need not be simultaneously raised above motor mount <b>68</b> for passing therethrough. Alternative embodiments of drive shafts that can be used in the present inventive system, including examples of how separate sections can be coupled together, are disclosed in U.S. Pat. No. 8,641,314 which issued on Feb. 4, 2014 and which is incorporated herein by specific reference.

As depicted in <figref idref="DRAWINGS">FIG. 5</figref>, impeller assembly <b>78</b> comprises an elongated first tubular connector <b>80</b> having rotational assembly <b>82</b> secured at one end and an elongated second tubular connector <b>84</b> coupled at the opposing end. A plurality of impellers <b>85</b>A-C are disposed along the length of second tubular connector <b>84</b>. More specifically, first tubular connector <b>80</b> has a first end <b>118</b> and an opposing second end <b>120</b> with an interior surface that bounds a passage <b>122</b> that extends along the length thereof. In one embodiment first tubular connector <b>80</b> comprises a flexible tube that can typically be bent along its length over an angle of 90° and more commonly 180° or 270° without plastic deformation. Tubular connector <b>80</b> is typically made from, comprises or consists of a sufficiently flexible material, such as an elastomeric material, so that tubular connector can withstand repeated bending and deformation without appreciable structural yield and can possess a durometer on the Shore 00 scale that is typically less than 98 and often less than 60 or 30. Other values can also be used. First tubular connector <b>80</b> can be formed from a polymeric material such as flexible PVC or other polymers having the desired properties.

Rotational assembly <b>82</b> comprises an outer casing <b>86</b> and a tubular hub <b>88</b> that centrally extends through outer casing <b>86</b> and is rotatably coupled thereto. One or more dynamic seals can be formed between outer casing <b>86</b> and tubular hub <b>88</b> so that a sterile seal can be maintained therebetween. Furthermore, one or more bearings can be positioned between outer casing <b>86</b> and tubular hub <b>88</b> to enable easy rotation of hub <b>88</b> relative to casing <b>86</b>. As depicted in <figref idref="DRAWINGS">FIG. 6</figref>, hub <b>88</b> has an interior surface <b>124</b> that bounds a passage <b>126</b> extending therethrough. At least a section of interior surface <b>124</b> forms an engaging portion <b>128</b> that is complementary to the transverse cross section of first driver portion <b>112</b> on drive shaft <b>72</b> (<figref idref="DRAWINGS">FIG. 5</figref>) or is otherwise configured to engage first driver portion <b>112</b> so that when first driver portion <b>112</b> is received within engaging portion <b>128</b>, rotation of drive shaft <b>72</b> facilitates rotation of hub <b>88</b> relative to casing <b>86</b>.

Returning to <figref idref="DRAWINGS">FIG. 5</figref>, hub <b>88</b> includes a barbed stem <b>89</b> that downwardly projects below casing <b>86</b>. Stem <b>89</b> is configured to be received within first end <b>118</b> of first tubular connector <b>80</b> so that a liquid tight seal is formed therebetween and so that stem <b>89</b> is secured to first tubular connector <b>80</b>. Casing <b>86</b> includes an annular, outwardly projecting flange <b>132</b> which, as depicted in <figref idref="DRAWINGS">FIG. 2</figref>, is welded or otherwise secured to container <b>12</b> so as to secure casing to container <b>12</b> within opening <b>52</b> thereof. In this configuration, first tubular connector <b>80</b> projects into compartment <b>50</b> of container <b>12</b>.

Returning to <figref idref="DRAWINGS">FIG. 5</figref>, second tubular connector <b>84</b> has a first end <b>136</b> and an opposing second end <b>138</b> with an interior surface <b>140</b> and an exterior surface <b>142</b> extending therebetween. Interior surface <b>140</b> bounds a passage <b>141</b> (<figref idref="DRAWINGS">FIG. 11</figref>) extending therethrough. In one embodiment, second tubular connector <b>84</b> is more rigid than first tubular connector <b>80</b>. For example, in different embodiments second tubular connector <b>84</b> cannot be bent along its length over an angle of 20°, 40°, 90° or 120° without plastic deformation. Tubular connector <b>84</b> is typically not made from and does not comprise or consist of an elastomeric material. Rather, tubular connector <b>84</b> is typically comprised of a rigid plastic or other material so that tubular connector <b>84</b> has a durometer on the Shore D scale that is typically greater than 20 and often greater than 40 or 60. Other values can also be used.

As depicted in <figref idref="DRAWINGS">FIG. 7</figref>, formed at first end <b>136</b> is a tapered stem <b>144</b> that is configured to be received within second end <b>120</b> of first tubular connector <b>80</b> (<figref idref="DRAWINGS">FIG. 5</figref>) so as to form a secure, liquid tight seal therebetween. A barbed stem <b>146</b> is formed at second end <b>138</b>. Exterior surface <b>84</b> extending between stems <b>144</b> and <b>146</b> has a transverse cross section that is polygonal, elliptical, or some other non-circular configuration. For example, the transverse cross section can be polygonal having 5, 6, 7 or more sides. Disposed at spaced apart locations along the length of exterior surface <b>142</b> are three pairs of annular grooves <b>148</b>A-C and <b>150</b>A-C that encircle second tubular connector <b>84</b>.

Exterior surface <b>142</b> of second tubular connector <b>84</b> is configured to receive impellers <b>85</b>A-C so that they can be fixed thereon. As used in the specification and appended claims, the term “impeller” is broadly intended to include all conventional types of impellers and impeller blades along with other structures that can be mounted on second tubular connector <b>84</b> so that when second tubular connector <b>84</b> is rotated within container <b>12</b>, the structures can uniformly mix the fluid within container <b>12</b>. In the current embodiment, as depicted in <figref idref="DRAWINGS">FIG. 8</figref>, each impeller <b>85</b> comprises a central hub <b>154</b> having a plurality of fins <b>156</b> outwardly projecting therefrom. Again, fins <b>156</b> can comprise any type of impeller blade that will function for mixing in the intended application. Hub <b>154</b> has an interior surface <b>158</b> that bounds an opening <b>160</b> extending therethrough. Interior surface <b>158</b> has a configuration complementary to exterior surface <b>142</b> of second tubular connector <b>84</b> or is otherwise configured to engage exterior surface <b>142</b> so that when second tubular connector <b>84</b> is advanced through opening <b>160</b> of impeller <b>85</b>, impeller <b>85</b> is keyed with or otherwise secured to second tubular connector <b>84</b> so that rotation of second tubular connector <b>84</b> along the longitudinal axis thereof causes impellers <b>85</b> to concurrently rotate therewith.

During assembly, each impeller <b>85</b>A-C is slid along second tubular connector <b>84</b> until hub <b>154</b> is centrally located between a pair of corresponding grooves <b>148</b> and <b>150</b>. Retainers <b>162</b> are received within grooves <b>148</b> and <b>150</b> to retain impellers <b>85</b> at the desired locations along second tubular connector <b>84</b>. In one embodiment, retainers <b>162</b> comprise O-rings that are made from an elastomeric material such as silicone. Other materials can also be used. The O-rings are configured so that when they are received within annular grooves <b>148</b>/<b>150</b>, the O-rings still radially outwardly project beyond exterior surface <b>142</b> of second tubular connector <b>84</b>. Thus, the O-rings can be slid onto second tubular connector <b>84</b> on opposing sides of each impeller <b>85</b> so that when the O-rings are received within annular grooves <b>148</b>/<b>150</b> with impeller <b>85</b> disposed therebetween, the O-rings preclude impeller from sliding along the length of second tubular connector <b>84</b> past the O-rings. This configuration provides a simple way to manufacture and assemble second tubular connector <b>84</b> with impellers thereon and eliminates complex molding procedures and mechanical fasteners, such as set screws, which can become loose or can form small holes or crevices into which cells or microorganisms can stagnate and die. The configuration also eliminates the required use of adhesives which can potentially leach into and contaminate a culture.

In alternative embodiments, it is appreciated that other retainers <b>162</b> can also be used. For example, snap rings or clips, such as those having a C-shaped configuration, could be received within grooves <b>148</b>/<b>150</b> to secure impellers <b>85</b>. In still other embodiments, it is appreciated that other conventional techniques, such as those discussed above, could be used to either permanently or removably secure impellers <b>85</b> to second tubular connector <b>84</b>. Furthermore, in other alternative embodiments it is appreciated that not all of exterior surface <b>142</b> of second tubular connector <b>84</b> needs to be complementary to interior surface <b>158</b> of impellers <b>85</b>. Rather, only the portion of exterior surface <b>142</b> between grooves <b>148</b> and <b>150</b> needs to have the complementary or otherwise engaging surface so as to mate with impellers <b>85</b>.

Turning to <figref idref="DRAWINGS">FIG. 10</figref>, an end cap <b>166</b>, such as made from a polymeric or elastomeric material, can be slid over stem <b>146</b> and secured by a fastener <b>168</b>, such as a pull tie or crimp, so as to form a liquid tight seal at second end <b>138</b> of second tubular connector <b>84</b>.

Turning to <figref idref="DRAWINGS">FIG. 11</figref>, interior surface <b>140</b> of second tubular connector <b>84</b> along the length thereof has a configuration that is complementary to the transverse cross section of second driver portion <b>114</b> on drive shaft <b>72</b> (<figref idref="DRAWINGS">FIG. 5</figref>) or is otherwise configured to engage second driver portion <b>114</b> so that when second driver portion <b>114</b> is received within passage <b>141</b> of second tubular connector <b>84</b>, rotation of drive shaft <b>72</b> facilitates concurrent rotation of second tubular connector <b>84</b>. For example, interior surface <b>140</b> of second tubular connector <b>84</b> and second driver portion <b>114</b> on drive shaft <b>72</b> can have complementary polygonal or other non-circular configurations.

It is appreciated that second driver portion <b>114</b> need not engage the full length of second tubular connector <b>84</b>. However, because drive shaft <b>72</b> is typically stronger than second tubular connector <b>84</b>, the more length of drive shaft <b>72</b> that directly engages along the length of second tubular connector <b>84</b>, the more strength is imparted to second tubular connector <b>84</b>. Thus, in general, in situations where greater torque will be applied to second tubular connector <b>84</b>, more length of second driver portion <b>114</b> should engage second tubular connector <b>84</b>. For example, second driver portion <b>114</b> can be configured to engage at least 20% and more commonly at least 40% or 60% of the total length of second tubular connector <b>84</b>. Other percentages can also be used.

During assembly, impeller assembly <b>78</b> is coupled with container <b>12</b> as discussed above. The assembly can then be sterilized, such as by radiation, so that compartment <b>50</b> and the components therein are sterile. To facilitate shipping and storage, container <b>12</b> can be folded over at any location along the length of flexible first tubular connector <b>80</b> so as to minimize the length and size of the container assembly. During use, container <b>12</b> with impeller assembly <b>78</b> secured thereto is positioned within chamber <b>30</b> of support housing <b>14</b>. Rotational assembly <b>82</b> is then removably connected to bottom surface <b>64</b> of housing <b>60</b> of drive motor assembly <b>59</b> so that hub <b>88</b> is aligned with motor mount <b>68</b>. First end <b>100</b> of drive shaft <b>72</b> is advanced down through motor mount <b>68</b>, through hub <b>86</b> of rotational assembly <b>82</b>, through first tubular connector <b>80</b> and finally into second tubular connector <b>84</b>.

In this position, drive shaft <b>72</b> is locked to motor mount <b>68</b> with first driver portion <b>112</b> engaging hub <b>88</b> and second driver portion <b>114</b> engaging second tubular connector <b>84</b>, as discussed above. As a result, rotation of motor mount <b>68</b> by motor <b>70</b> facilitates rotation of drive shaft <b>72</b> which in turn facilitates the concurrent rotation of hub <b>88</b>, first tubular connector <b>80</b>, second tubular connector <b>84</b>, and impellers <b>85</b> mounted on second tubular connector <b>84</b>. In turn, rotation of impeller <b>85</b> facilities mixing and suspension of the fluid within compartment <b>50</b> of container <b>12</b>. Further disclosure with regard to drive motor assembly <b>59</b>, rotational assembly <b>82</b>, and drive shaft <b>72</b> and how these elements operate and couple together, along with alternative embodiments thereof, is disclosed in United States Patent Publication Nos. 2011-0188928 A1, published Aug. 4, 2011; 2011-0310696, published Dec. 22, 2011 and 2006-0280028, published Dec. 14, 2006 which are incorporated herein by specific reference.

Embodiments of the inventive system have a number of advantages. For example, by using second tubular connector <b>84</b> which is rigid, a plurality of impellers can be mounted thereon which significantly increases the ability to mix the fluid within container <b>12</b>. This is significantly helpful in situations such as where the fluid processing system is functioning as a fermentor for growing microorganisms. This is because fermentors typically require aggressive mixing to achieve and maintain the needed gas-liquid mass transfer with the fluid to keep the microorganisms alive and thriving. The system is also advantageous in that the container assembly is easy to manufacture, scalable, and disposable after use so that no cleaning or sterilization is required. As discussed above, by using first tubular connector <b>80</b> which is flexible, the container assembly can still be folded into a relatively small volume, thereby making it easier to sterilize, ship, and store. Furthermore, the system provides an easy, modular system for attaching impellers to second tubular connector <b>84</b>. For example, different systems having different numbers of impellers can be designed using the same second tubular connector <b>84</b>. In addition, because all of the impellers can be mounted on second tubular connector <b>84</b>, only one separate connection to first tubular connector <b>80</b> is required, thereby simplifying assembly and minimizing locations for potential contamination. Other advantages also exist.

It is appreciated that the inventive system also has a number of alternative embodiments. For example, although second tubular connector <b>84</b> is shown having three impellers <b>85</b> mounted thereon, in other embodiments second tubular connector <b>84</b> can have 1, 2, 4, 5 or more impellers <b>85</b> mounted along the length thereof. It is also appreciated that the relative lengths of first tubular connector <b>80</b> and second tubular connector <b>84</b> can be varied. For example, in some embodiments, the length of second tubular connector <b>84</b> is at least 20%, 40% or 60% of the combined total length of first tubular connector <b>80</b> and second tubular connector <b>84</b>. In other embodiments, the length of first tubular connector <b>80</b> is at least 20%, 40% or 60% of the combined total length of first tubular connector <b>80</b> and second tubular connector <b>84</b>.

Depicted in <figref idref="DRAWINGS">FIG. 12</figref> is an alternative embodiment of a drive shaft <b>72</b>A. Like features between drive shaft <b>72</b> and <b>72</b>A are identified by like reference characters. Drive shaft <b>72</b>A is substantially identical to drive shaft <b>72</b> except that first driver portion <b>112</b> (<figref idref="DRAWINGS">FIG. 5</figref>) has been eliminated. As such, drive shaft <b>72</b> does not directly engage hub <b>88</b>. However, hub <b>88</b> can still rotate by torque produced by first tubular connector <b>80</b>.

The present invention may be embodied in other specific forms without departing from its spirit or essential characteristics. The described embodiments are to be considered in all respects only as illustrative and not restrictive. The scope of the invention is, therefore, indicated by the appended claims rather than by the foregoing description. All changes which come within the meaning and range of equivalency of the claims are to be embraced within their scope.